{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T14:00:07Z","timestamp":1782396007964,"version":"3.54.5"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2017,6,19]],"date-time":"2017-06-19T00:00:00Z","timestamp":1497830400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2017,6,19]],"date-time":"2017-06-19T00:00:00Z","timestamp":1497830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2017,8]]},"abstract":"\n The etiopathogenesis of primary sclerosing cholangitis is unknown. Genetic variants of fucosyltransferase 2 (FUT2) have been identified in genome\u2010wide association studies as risk factors for primary sclerosing cholangitis. We investigated the role of Fut2 in murine liver pathophysiology by studying\n Fut2\u2013\/\u2013<\/jats:italic>\n mice.\n Fut2\u2013\/\u2013<\/jats:italic>\n mice were viable and fertile, had lower body weight than wild\u2010type (wt) littermates and gray fur. Half of the\n Fut2\u2013\/\u2013<\/jats:italic>\n mice showed serum bile salt levels 40 times higher than wt (\n Fut2\u2013\/\u2013<\/jats:italic>\n high<\/jats:sup>\n ), whereas the remainder were normocholanemic (\n Fut2\u2013\/\u2013<\/jats:italic>\n low<\/jats:sup>\n ).\n Fut2\u2013\/\u2013<\/jats:italic>\n mice showed normal serum liver tests, bile flow, biliary bile salt secretion, fecal bile salt loss, and expression of major hepatocellular bile salt transporters and cytochrome P450 7a1, the key regulator of bile salt synthesis, indicating that elevated serum bile salts in\n Fut2\u2013\/\u2013<\/jats:italic>\n high<\/jats:sup>\n mice were not explained by cholestasis.\n Fut2\u2013\/\u2013<\/jats:italic>\n high<\/jats:sup>\n mice, but not\n Fut2\u2013\/\u2013<\/jats:italic>\n low<\/jats:sup>\n mice, were sensitive to hydrophobic bile salt feeding (0.3% glycochenodeoxycholate); they rapidly lost weight and showed elevation of serum liver tests (alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase) and areas of liver parenchymal necrosis. Histomorphological evaluation revealed the presence of paraportal shunting vessels, increased numbers of portal vascular structures, wall thickening of some portal arteries, and periductal fibrosis in\n Fut2\u2013\/\u2013<\/jats:italic>\n high<\/jats:sup>\n mice more than\n Fut2\u2013\/\u2013<\/jats:italic>\n low<\/jats:sup>\n mice and not wt mice. Unconjugated bilirubin and ammonia were or tended to be elevated in\n Fut2\u2013\/\u2013<\/jats:italic>\n high<\/jats:sup>\n mice only. Portosystemic shunting was demonstrated by portal angiography, which disclosed virtually complete portosystemic shunting in\n Fut2\u2013\/\u2013<\/jats:italic>\n high<\/jats:sup>\n mice, discrete portosystemic shunting in\n Fut2\u2013\/\u2013<\/jats:italic>\n low<\/jats:sup>\n mice, and no shunting in wt littermates.\n Conclusion<\/jats:italic>\n : Liver pathology in\n Fut2\u2013\/\u2013<\/jats:italic>\n mice is dominated by consequences of portosystemic shunting resulting in microcirculatory disturbances, mild (secondary) periductal fibrosis, and sensitivity toward human bile salt toxicity. (H\n epatology<\/jats:sc>\n 2017;66:542\u2013554).\n <\/jats:p>","DOI":"10.1002\/hep.29029","type":"journal-article","created":{"date-parts":[[2017,1,5]],"date-time":"2017-01-05T18:06:52Z","timestamp":1483639612000},"page":"542-554","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":36,"title":["Knockout of the primary sclerosing cholangitis\u2010risk gene Fut2 causes liver disease in mice"],"prefix":"10.1097","volume":"66","author":[{"given":"Luca","family":"Maroni","sequence":"first","affiliation":[{"name":"Department of Gastroenterology & Hepatology and Tytgat Institute for Liver and Intestinal Research, Academic Medical Center,University of Amsterdam,Amsterdam,The Netherlands"},{"name":"Department of Gastroenterology,Universit\u00e0 Politecnica delle Marche,Ancona,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon D.","family":"Hohenester","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology & Hepatology and Tytgat Institute for Liver and Intestinal Research, Academic Medical Center,University of Amsterdam,Amsterdam,The Netherlands"},{"name":"Department of Medicine II,University of Munich (LMU),Munich,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stan F.J.","family":"van de Graaf","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology & Hepatology and Tytgat Institute for Liver and Intestinal Research, Academic Medical Center,University of Amsterdam,Amsterdam,The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"Tolenaars","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology & Hepatology and Tytgat Institute for Liver and Intestinal Research, Academic Medical Center,University of Amsterdam,Amsterdam,The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krijn","family":"van Lienden","sequence":"additional","affiliation":[{"name":"Department of Radiology,Academic Medical Center,Amsterdam,The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Verheij","sequence":"additional","affiliation":[{"name":"Department of Pathology,Academic Medical Center,Amsterdam,The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Marzioni","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Universit\u00e0 Politecnica delle Marche,Ancona,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom H.","family":"Karlsen","sequence":"additional","affiliation":[{"name":"Norwegian PSC Research Center and Section for Gastroenterology,Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital,Rikshospitalet,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald P.J.","family":"Oude Elferink","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology & Hepatology and Tytgat Institute for Liver and Intestinal Research, Academic Medical Center,University of Amsterdam,Amsterdam,The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Beuers","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology & Hepatology and Tytgat Institute for Liver and Intestinal Research, Academic Medical Center,University of Amsterdam,Amsterdam,The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2017,6,19]]},"reference":[{"key":"hep29029-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1016\/S0140-6736(13)60096-3","article-title":"Primary sclerosing 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Its appearance after bile\u2010duct ligation in rats with a portacaval shunt","volume":"106","year":"1982","journal-title":"Arch Pathol Lab Med"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.29029","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-201708000-00023","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T21:40:49Z","timestamp":1749850849000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-201708000-00023"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,19]]},"references-count":44,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2017]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.29029","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.727169485.793536149","asserted-by":"object"}]},"ISSN":["0270-9139","1527-3350"],"issn-type":[{"value":"0270-9139","type":"print"},{"value":"1527-3350","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,19]]},"assertion":[{"value":"2016-06-29","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-01-03","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}